The ATP6 protein functions as a hydrogen ion channel that couples ion transport with rotary ATP catalysis. Missense mutations in the human ATP6 gene are believed to cause at least three related and devastating syndromes characterized by progressive muscle impairment and neurological symptoms: NARP (neuropathy, ataxia, and retinitis pigmentosa), MILS (maternally inherited Leigh's syndrome) and FBSN (familial bilateral striatal necrosis) and contribute to the pathogenesis of several other age-related diseases. We have isolated a missense mutation within the mitochondrial ATP6 gene of Drosophila and developed this as model of mitochondrial encephalomyopathy. We propose to utilize this genetic animal model system to elucidate the pathophysiological basis for progressive encephalomyopathies in vivo. PUBLIC HEALTH RELEVANCE: Mitochondrial disease affect ~ 1 in 4000 individuals. Currently there exists no effective pharmacotherapy for these devastating diseases. Our understanding of disease pathogenesis of these progressive conditions is limited, in large part due to a lack of animal models of these diseases. Our model system captures many relevant features of these diseases in an amenable genetic system and this proposal aims to study pathogenesis of these diseases.